Tryptase is a major protease in human mast cells. Evidence indicates that tryptase may be important in neuropeptide processing and tissue inflammation in the lungs. The purpose of this study is to synthesize three analogs of an initial aromatic amidine tryptase inhibitor BABIM [bis(5-amidino-2-benzimidazolyl) methane] and determine their activity in cellular and ex vivo bioassays. The ability of the compounds to inhibit tryptase in a biochemical assay as well as the tryptase-mediated hydrolysis of bronchoactive peptides and tryptase-mediated stimulation of fibroblast mitogenesis in vitro will be determined. In addition, the ability of the most promising compound to prevent in vivo airway hyperresponsiveness in a dog model of asthma will be determined. Molecular modeling techniques will be used to continue the design of new analogs with increased activity against tryptase. These studies will determine if the development of tryptase inhibitors will be potentially useful for the treatment of airway hyperresponsiveness of asthma. GRAMT=R43HL57695 DESCRIPTION (Adapted from applicant's abstract): This project will develop an oxide-glass infrared fiber with improved mechanical strength and transmission, for use with the 2.9 micron Er:YAG laser. This laser is ideal for use for laser angioplasty since it offers precise tissue ablation with little thermal necrosis and can ablate even heavily calcified plaque. In order to prevent fiber breakage at sharp bends or kinks in the artery, they will improve the fiber strength by optimizing the glass composition and develop an extruded plastic coating. In addition, since long fiber lengths of about 3 meters will be used, they will improve the transmission by reducing OH impurities, develop oxide glasses with a shifted infrared edge, and reduce scattering defects. This improved fiber will then be tested for power handling using an in-house Er:YAG laser.